Analysis of AMPA Receptor Properties During Postnatal Development of Mouse Hippocampal Astrocytes

Abstract

Seifert, Gerald, Min Zhou, and Christian Steinhäuser. Analysis of AMPA receptor properties during postnatal development of mouse hippocampal astrocytes. J. Neurophysiol. 78: 2916–2923, 1997. Glial cells in the mammalian brain express various types of voltage- and ligand-gated ion channels, including glutamate receptors (GluRs) of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-subtype. In the present study we followed developmental changes in the functional properties of AMPA receptor (AMPA-R) channels expressed by astrocytes of the mouse hippocampus between postnatal days (P) 5–35 to learn more about the physiological significance of these glial receptors. A fast concentration clamp technique was applied to cells acutely isolated from the CA1 stratum radiatum subregion to quantitatively analyze rapidly activating and desensitizing receptor responses. The equilibrium responses of glutamate and kainate differed between P5 and P12. Although the maximum current induced by kainate was almost the same at all developmental stages, a steep rise in the maximum glutamate response was observed within the same time range. Between P5 and P12 there was an increase in the potentiation of AMPA-R currents with cyclothiazide (CTZ); at the same time, the dissociation kinetics of CTZ became significantly slower. These changes in the pharmacological properties suggested a variation in splice variant expression. With proceeding maturation, we observed an increase in the degree of desensitization of the glutamate- and AMPA-induced receptor currents. In addition to the shift in flip/flop splicing, these findings could hint at a developmental regulation of RNA editing in the arginine/glycine site. Altogether, the present results demonstrate changes in astrocytic AMPA-R functioning early in postnatal development, although after P12 the receptor properties remained almost constant. Although the overall Ca2+ permeability did not vary during development, the prolonged receptor opening in the early postnatal period causes an enhanced Na+/Ca2+ influx into the immature astrocytes. This could influence glial proliferation and differentiation during CNS ontogenesis.